p73 competes with p53 and attenuates its response in a human ovarian cancer cell line

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Abstract

The transcriptional activity of the p53 tumor suppressor protein is crucial for the regulation of cell growth, apoptosis and tumor progression. The first identified p53 relative, p73, was reported to be monoallelically expressed in normal tissues. In some tumors, loss of heterozygosity was associated with overexpression of the silent allele. Human p73α was transfected into the wild-type p53-expressing human ovarian carcinoma cell line A2780. Unlike human osteosarcoma Saos-2 cells, A2780 cells could tolerate hyperexpression of p73α and clones overexpressing p73α could be isolated. No p53-p73 protein-protein interaction was found in these clones in co-immunoprecipitation experiments. Endogenous p53 transcriptional activity was markedly decreased both when p73 was integrated into the genome and in transient transfections using a reporter plasmid containing the p53 binding site linked to luciferase. Transient transfection of p73 with a mutation in the DNA-binding domain did not show these effects. The competition for p53 DNA binding by p73α was also evident in gel shift experiments. The results suggest that p73 can modulate p53 function by inhibiting its DNA binding and that overexpression of p73 in tumors might be a novel mechanism of inactivation of p53.

Original languageEnglish
Pages (from-to)513-519
Number of pages7
JournalNucleic Acids Research
Volume28
Issue number2
Publication statusPublished - Jan 15 2000

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Ovarian Neoplasms
Cell Line
Transfection
DNA
Clone Cells
Tumor Suppressor Protein p53
Neoplasms
Loss of Heterozygosity
Osteosarcoma
Luciferases
Immunoprecipitation
Plasmids
Gels
Alleles
Binding Sites
Genome
Apoptosis
Carcinoma
Mutation
Growth

ASJC Scopus subject areas

  • Genetics

Cite this

p73 competes with p53 and attenuates its response in a human ovarian cancer cell line. / Vikhanskaya, Faina; D'Incalci, Maurizio; Broggini, Massimo.

In: Nucleic Acids Research, Vol. 28, No. 2, 15.01.2000, p. 513-519.

Research output: Contribution to journalArticle

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